In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 259-259
Abstract:
259 Background: Ganetespib is an Hsp90 inhibitor that downregulates EGFR, VEGFR, HER2, MET, IGF-IR, and other Hsp90 client proteins involved in hepatocarcinogenesis, thereby making it an attractive therapy for HCC. This multicenter Phase I study was performed to establish the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary activity of ganetespib in patients with advanced HCC. Methods: Thirteen patients with advanced HCC, Child-Pugh A or B cirrhosis, progression on or intolerance to sorafenib, and ECOG PS ≤ 1 were enrolled in a standard 3x3 dose escalation study at ganetespib doses of 100 mg/m 2 , 150 mg/m 2 , and 200 mg/m 2 IV given on days 1, 8, and 15 of a 28 day cycle. RECIST 1.1 response was evaluated by CT/MRI every 8 weeks. The primary objective was to determine the RP2D, and secondary objectives included assessments of safety, toxicity, pharmacokinetics, median time to progression (TTP), median progression-free survival (PFS), median overall survival (OS), and objective response rate (ORR). Results: Twelve of the 13 patients enrolled received study drug, and enrollment is ongoing for the 200 mg/m 2 cohort. Of the 12 patients: male 66%; median age 57 years; median number of prior treatments 2; Asian 33%; HCC etiology (HBV 41.7%, HCV 41.7%, hemachromatosis 8.3%, unknown 16.7%); median baseline AFP 115.3 ng/mL. Median TTP for the 10 evaluable patients was 49 days (1.6 months). No responses were seen, but 2/10 (20.0%) patients had stable disease at 8 weeks. AFP response, defined as reduction from baseline of 〉 50% in patients with an elevated baseline AFP, was seen in 0% of patients. Most common AEs: diarrhea (100%), AST elevation (58.3%), hyperglycemia (58.3%), and fatigue (58.3%). Most common Gr 3/4 AEs: hyperglycemia (25%), anemia (16.7%), lipasemia (16.7%), and ALKP elevation (16.7%). One (8.3%) patient had a fatal AE, septic shock, within 30 days of receiving the drug. One DLT was observed: Gr 3 lipasemia at the 100mg/m 2 dose. Conclusions: Ganetespib had a manageable safety profile and demonstrated limited efficacy in patients with advanced HCC. Determination of the R2PD, further assessment of clinical efficacy, and analysis of molecular markers are still pending, and a follow-up Phase II study will be considered based on this data. Clinical trial information: NCT01665937.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.4_suppl.259
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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